RESUMO
We report the case of a female found to have mosaicism for mutation in the STK11 gene, with the mutant allele expressed in her gametes, evident by her affected offspring, and in her gastrointestinal tract demonstrated on an excised polyp analysed for diagnosis. Mosaicism for Peutz-Jeghers syndrome (PJS) has been reported in a small number of cases previously but a clinical presentation such as this has not previously been described. This finding of mosaicism was several years after initial investigations failed to identify the same STK11 mutation in this woman whose son was diagnosed with PJS at a young age. This case highlights the importance of considering mosaicism as an explanation for apparent de novo cases of PJS syndrome. It also has implications for genetic counselling, predictive testing and cancer screening.
Assuntos
Pólipos Intestinais/genética , Mosaicismo , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Criança , Colonoscopia , Feminino , Testes Genéticos , Humanos , Íleo/diagnóstico por imagem , Íleo/patologia , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Mães , Mutação , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/patologiaRESUMO
AIMS/HYPOTHESIS: Phosphatidylinositol 3-OH kinases (PI3Ks) regulate beta cell mass, gene transcription, and function, although the contribution of the specific isoforms is unknown. As reduced type 1A PI3K signalling is thought to contribute to impaired insulin secretion, we investigated the role of the type 1A PI3K catalytic subunits α and ß (p110α and -ß) in insulin granule recruitment and exocytosis in rodent and human islets. METHODS: The p110α and p110ß subunits were inhibited pharmacologically or by small hairpin (sh)RNA-mediated knockdown, and were directly infused or overexpressed in mouse and human islets, beta cells and INS-1 832/13 cells. Glucose-stimulated insulin secretion (GSIS), single-cell exocytosis, Ca(2+) signalling, plasma membrane granule localisation, and actin density were monitored. RESULTS: Inhibition or knockdown of p110α increased GSIS. This was not due to altered Ca(2+) responses, depolymerisation of cortical actin or increased cortical granule density, but to enhanced Ca(2+)-dependent exocytosis. Intracellular infusion of recombinant PI3Kα (p110α/p85ß) blocked exocytosis. Conversely, knockdown (but not pharmacological inhibition) of p110ß blunted GSIS, reduced cortical granule density and impaired exocytosis. Exocytosis was rescued by direct intracellular infusion of recombinant PI3Kß (p110ß/p85ß) even when p110ß catalytic activity was inhibited. Conversely, both the wild-type p110ß and a catalytically inactive mutant directly facilitated exocytosis. CONCLUSIONS/INTERPRETATION: Type 1A PI3K isoforms have distinct and opposing roles in the acute regulation of insulin secretion. While p110α acts as a negative regulator of beta cell exocytosis and insulin secretion, p110ß is a positive regulator of insulin secretion through a mechanism separate from its catalytic activity.
Assuntos
Classe Ia de Fosfatidilinositol 3-Quinase/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Animais , Sinalização do Cálcio , Domínio Catalítico , Membrana Celular/metabolismo , Inibidores Enzimáticos/farmacologia , Exocitose , Humanos , Secreção de Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Isoformas de Proteínas/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
We report a familial adenomatous polyposis patient with a known truncating mutation on exon 15 of the APC gene who developed an invasive follicular thyroid cancer in addition to multiple intra-cranial and spinal desmoids. This combination of manifestations has not previously been recorded in the literature.
Assuntos
Polipose Adenomatosa do Colo/complicações , Neoplasias do Sistema Nervoso Central/etiologia , Fibromatose Agressiva/etiologia , Segunda Neoplasia Primária/etiologia , Neoplasias da Glândula Tireoide/etiologia , Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Neoplasias do Sistema Nervoso Central/patologia , Criança , Éxons/genética , Fibromatose Agressiva/patologia , Humanos , Masculino , Mutação/genética , Segunda Neoplasia Primária/patologia , Prognóstico , Neoplasias da Glândula Tireoide/patologiaRESUMO
AIM: Patients with germline phosphatase and tensin homologue (PTEN) mutations develop hamartomatous lesions in several organs and are at increased risk of various malignancies. We assessed the lifetime risk of benign and malignant gastrointestinal lesions in patients with a proven PTEN mutation. METHOD: Data on gender, mutation, dates of birth, last contact, and diagnosis, location and type of gastrointestinal lesions were collected from nine countries. The lifetime risk of gastrointestinal lesions was calculated by Kaplan-Meier methods. RESULTS: A total of 156 patients (67 men, 43%) from 101 families with a PTEN mutation were included. Patients were born between 1928 and 2008. Benign gastrointestinal polyps were reported in 49 (31%) patients at a mean age of 38 years (range 18-62 years) and were most often hamartomas. Twenty-two (44%) patients had upper as well as lower gastrointestinal lesions, 14 (29%) had only colonic lesions and 13 (27%) had gastrointestinal lesions at unknown sites. The cumulative risk of developing benign gastrointestinal polyps was 70% at age 60. Four patients (two men) developed colorectal carcinoma at 53, 57, 59 and 62 years, respectively. The cumulative risk of developing colorectal carcinoma was 18% at age 60. Except for one carcinoid in the small intestine, no upper gastrointestinal cancers were observed. CONCLUSION: Benign gastrointestinal lesions are common in PTEN mutation carriers, and a three- to four-fold increased lifetime risk of colorectal cancer compared with the general population may exist. Colorectal screening of patients with germline PTEN mutations is recommended, starting at age 40 years.
Assuntos
Pólipos do Colo/genética , Neoplasias Colorretais/genética , Síndrome do Hamartoma Múltiplo/genética , PTEN Fosfo-Hidrolase/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Pólipos do Colo/etiologia , Neoplasias Colorretais/etiologia , Feminino , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndrome do Hamartoma Múltiplo/complicações , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS/HYPOTHESIS: It is thought that the voltage-dependent potassium channel subunit Kv2.1 (Kv2.1) regulates insulin secretion by controlling beta cell electrical excitability. However, this role of Kv2.1 in human insulin secretion has been questioned. Interestingly, Kv2.1 can also regulate exocytosis through direct interaction of its C-terminus with the soluble NSF attachment receptor (SNARE) protein, syntaxin 1A. We hypothesised that this interaction mediates insulin secretion independently of Kv2.1 electrical function. METHODS: Wild-type Kv2.1 or mutants lacking electrical function and syntaxin 1A binding were studied in rodent and human beta cells, and in INS-1 cells. Small intracellular fragments of the channel were used to disrupt native Kv2.1-syntaxin 1A complexes. Single-cell exocytosis and ion channel currents were monitored by patch-clamp electrophysiology. Interaction between Kv2.1, syntaxin 1A and other SNARE proteins was probed by immunoprecipitation. Whole-islet Ca(2+)-responses were monitored by ratiometric Fura red fluorescence and insulin secretion was measured. RESULTS: Upregulation of Kv2.1 directly augmented beta cell exocytosis. This happened independently of channel electrical function, but was dependent on the Kv2.1 C-terminal syntaxin 1A-binding domain. Intracellular fragments of the Kv2.1 C-terminus disrupted native Kv2.1-syntaxin 1A interaction and impaired glucose-stimulated insulin secretion. This was not due to altered ion channel activity or impaired Ca(2+)-responses to glucose, but to reduced SNARE complex formation and Ca(2+)-dependent exocytosis. CONCLUSIONS/INTERPRETATION: Direct interaction between syntaxin 1A and the Kv2.1 C-terminus is required for efficient insulin exocytosis and glucose-stimulated insulin secretion. This demonstrates that native Kv2.1-syntaxin 1A interaction plays a key role in human insulin secretion, which is separate from the channel's electrical function.
Assuntos
Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Canais de Potássio Shab/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Eletrofisiologia , Humanos , Immunoblotting , Imunoprecipitação , Secreção de Insulina , Camundongos , Ligação Proteica , Ratos , Canais de Potássio Shab/genética , Sintaxina 1/metabolismoRESUMO
OBJECTIVE: To evaluate the role of targeted prostate cancer screening in men with BRCA1 or BRCA2 mutations, an international study, IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls), was established. This is the first multicentre screening study targeted at men with a known genetic predisposition to prostate cancer. A preliminary analysis of the data is reported. PATIENTS AND METHODS: Men aged 40-69 years from families with BRCA1 or BRCA2 mutations were offered annual prostate specific antigen (PSA) testing, and those with PSA > 3 ng/mL, were offered a prostate biopsy. Controls were men age-matched (± 5 years) who were negative for the familial mutation. RESULTS: In total, 300 men were recruited (205 mutation carriers; 89 BRCA1, 116 BRCA2 and 95 controls) over 33 months. At the baseline screen (year 1), 7.0% (21/300) underwent a prostate biopsy. Prostate cancer was diagnosed in ten individuals, a prevalence of 3.3%. The positive predictive value of PSA screening in this cohort was 47·6% (10/21). One prostate cancer was diagnosed at year 2. Of the 11 prostate cancers diagnosed, nine were in mutation carriers, two in controls, and eight were clinically significant. CONCLUSIONS: The present study shows that the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer. These results support the rationale for continued screening in such men.
Assuntos
Detecção Precoce de Câncer/métodos , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença/genética , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Adulto , Idoso , Detecção Precoce de Câncer/normas , Métodos Epidemiológicos , Predisposição Genética para Doença/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias da Próstata/sangue , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genéticaRESUMO
Familial gastrointestinal stromal tumours (GISTs) are rare but otherwise well-characterized tumour syndromes, most commonly occurring on a background of germline-activating mutations in the tyrosine kinase receptor c-KIT. The associated clinical spectrum reflects the constitutive activation of this gene product across a number of cell lines, generating gain-of-function phenotypes in interstitial cells of Cajal (GIST and dysphagia), mast cells (mastocytosis) and melanocytes (hyperpigmentation). We report a three-generation kindred harbouring a c-KIT germline-activating mutation resulting in multifocal GISTs, dysphagia and a complex melanocyte hyperpigmentation and hypopigmentation disorder, the latter with features typical of those observed in Waardenburg type 2 syndrome (WS2F). Sequencing of genes known to be causative for WS [microphthalmia transcription factor (MITF), Pax3, Sox10, SNAI2 ] failed to show any candidate mutations to explain this complex cutaneous depigmentation phenotype. Our case report conclusively expands the clinical spectrum of familial GISTs and shows a hitherto unrecognized link to WS. Possible mechanisms responsible for this novel cause of WS2F will be discussed.
Assuntos
Tumores do Estroma Gastrointestinal/genética , Síndromes Neoplásicas Hereditárias/genética , Síndrome de Waardenburg/genética , Alelos , Transtornos de Deglutição/genética , Transtornos de Deglutição/patologia , Tumores do Estroma Gastrointestinal/patologia , Mutação em Linhagem Germinativa , Humanos , Hiperplasia , Células Intersticiais de Cajal/patologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Plexo Mientérico/patologia , Síndromes Neoplásicas Hereditárias/patologia , Linhagem , Fenótipo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Análise de Sequência de DNA , Síndrome de Waardenburg/patologiaRESUMO
The genetic predisposition Peutz-Jeghers Syndrome (PJS) has been shown to be associated with mutations in the serine threonine kinase 11 (STK11) gene but only a proportion of probands have been shown to harbour changes in the gene. The remaining patients were proposed to be either associated with a second PJS gene or they harboured more cryptic mutations within the STK11 gene itself. With the introduction of the multiplex ligation probe amplification (MLPA) assay, large sequence losses or gains can be more readily identified. In this report we have screened 33 PJS patients from unrelated families, employing a combination of denaturing high-performance liquid chromatography, direct DNA sequencing and the MLPA assay to identify deleterious changes in the STK11 gene. The results revealed that 24 (73%) of patients diagnosed with PJS-harboured pathogenic mutations in the STK11 gene, including 10 (36%) with exonic or whole-gene deletions. No phenotypic differences were identified in patients harbouring large deletions in the STK11 gene compared to patients harbouring missense or nonsense mutations. Mutation analysis in PJS should include techniques such as MLPA to identify large exonic or whole-gene deletions and rearrangements. The high proportion of families with identifiable mutations in the STK11 gene using this range of techniques suggests that most, if not all PJS, is attributable to mutations in the STK11 gene, perhaps including as yet undiscovered changes in promoter or enhancer sequences or other cryptic changes.
Assuntos
Mutação , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Adolescente , Adulto , Austrália , Criança , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Deleção de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Técnicas de Amplificação de Ácido Nucleico , Síndrome de Peutz-Jeghers/enzimologia , Deleção de SequênciaRESUMO
BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by germline STK11 mutations and characterised by gastrointestinal polyposis. Although small bowel intussusception is a recognised complication of PJS, risk varies between patients. OBJECTIVE: To analyse the time to onset of intussusception in a large series of PJS probands. METHODS: STK11 mutation status was evaluated in 225 PJS probands and medical histories of the patients reviewed. RESULTS: 135 (60%) of the probands possessed a germline STK11 mutation; 109 (48%) probands had a history of intussusception at a median age of 15.0 years but with wide variability (range 3.7 to 45.4 years). Median time to onset of intussusception was not significantly different between those with identified mutations and those with no mutation detected, at 14.7 years and 16.4 years, respectively (log-rank test of difference, chi(2) = 0.58, with 1df; p = 0.45). Similarly no differences were observed between patient groups on the basis of the type or site of STK11 mutation. CONCLUSIONS: The risk of intussusception in PJS is not influenced by STK11 mutation status.
Assuntos
Intussuscepção/genética , Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
We assessed the efficacy of a comprehensive programme for stopping smoking in 210 smokers scheduled for surgery, before admission and 3 months after attending a pre-operative clinic. Participants were randomly allocated to receive an intervention incorporating nicotine replacement therapy for patients smoking more than 10 cigarettes per day ("dependent smokers"), or to a control group to receive usual care. Dependent smokers allocated to the intervention group were more likely to report abstinence before surgery than those allocated to receive usual-care (63 (73%) vs. 29 (56%), respectively; OR 2.2 (95% CI 1.0-4.8)), and 3 months after attendance (16 (18%) vs. 3 (5%), respectively; OR = 3.9 (95% CI 1.0-21.7).
Assuntos
Cuidados Pré-Operatórios/métodos , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Adulto , Idoso , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Nicotina/uso terapêutico , Agonistas Nicotínicos/uso terapêutico , Cuidados Pré-Operatórios/economia , Avaliação de Programas e Projetos de Saúde , Abandono do Hábito de Fumar/economia , Tabagismo/reabilitação , Resultado do TratamentoRESUMO
Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant, inherited condition that is characterized primarily by the development of early-onset colorectal cancer and a number of other epithelial malignancies. The underlying genetic basis of the disease is associated with a breakdown of DNA-mismatch repair. There are many genes involved in DNA-mismatch repair, and five of them have been implicated in HNPCC. Two of the genes (hMSH2 and hMLH1) account for the majority of HNPCC families (approximately 60%), and it is not known what the exact contributions of the remaining three genes (hPMS1, hPMS2, and hMSH6) are in relation to this condition. In addition, a sixth gene (hEXO1) has been associated with a disease phenotype that is consistent with HNPCC. Current estimates suggest that all four of these genes, combined, may account for up to 5% of families. In this report, we examine the contribution of hPMS2 and hEXO1 to a well-defined set of families that fulfill the diagnostic criteria for HNPCC. The genes, hPMS2 and hEXO1, were studied by denaturing high performance liquid chromatography (DHPLC) analysis in 21 families that have previously been determined not to have mutations in hMSH2 or hMLH1. hPMS2 accounts for a small proportion of HNPCC families, and none were deemed to be associated with hEXO1. Mutations in hPMS2 appear to account for a small proportion of families adhering to the Amsterdam II criteria, whereas hEXO1 does not appear to be associated with HNPCC.
Assuntos
Adenosina Trifosfatases/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Exodesoxirribonucleases/genética , Mutação/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Proteínas de Transporte , Cromatografia Líquida de Alta Pressão , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Análise Mutacional de DNA , Primers do DNA , Reparo do DNA/genética , Saúde da Família , Predisposição Genética para Doença/genética , Humanos , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento , Epidemiologia Molecular , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares , Proteínas Proto-Oncogênicas/genéticaRESUMO
OBJECTIVE: The consumption of cruciferous vegetables has a protective effect on the development of colorectal cancer. The phytochemical Sulforaphane is an isothiocyanate found almost exclusively in cruciferous vegetables. We have studied the effect of Sulforaphane on cell proliferation of an HT-29 colon cancer cell line. MATERIALS AND METHODS: HT-29 colon cancer cells were cultured in 96-well microtitre plates. Sulforaphane (in concentrations ranging from 0.01 to 0.1 mmol) were added to the wells. Cell proliferation was measured using the colourimetric assay technique. RESULTS: The proliferation of colon cancer cells was significantly reduced by Sulforaphane at concentrations of >/=0.02 mmol. CONCLUSION: These findings may help explain the epidemiologically proven protective effect of vegetables against colon cancer.
Assuntos
Anticarcinógenos/uso terapêutico , Neoplasias do Colo/prevenção & controle , Células HT29/efeitos dos fármacos , Tiocianatos/uso terapêutico , Anticarcinógenos/farmacologia , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Humanos , Isotiocianatos , Sulfóxidos , Tiocianatos/farmacologiaRESUMO
The occurrence of duodenal polyposis is well recognized in familial adenomatous polyposis. Lymphoid hyperplasia in association with familial adenomatous polyposis usually occurs in the terminal ileum, but it can occur in the duodenum and may be endoscopically difficult to distinguish from an adenoma. A case report is presented in which a 54-year-old male with familial adenomatous polyposis, who 20 years earlier had a subtotal colectomy and ileorectal anastomosis, presented with a large rectal villous tumor and was found to have a duodenal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The role of lymphoid hyperplasia in the development of mucosa-associated lymphoid tissue lymphoma is discussed, as well as the issue of mucosa-associated lymphoid tissue lymphoma in familial adenomatous polyposis. In cases in which biopsies of polypoid lesions in patients with familial adenomatous polyposis show dense lymphoid aggregates, flow cytometry may assist in the diagnosis.
Assuntos
Polipose Adenomatosa do Colo/complicações , Polipose Adenomatosa do Colo/cirurgia , Neoplasias Duodenais/etiologia , Neoplasias Duodenais/patologia , Íleo/cirurgia , Linfoma de Zona Marginal Tipo Células B/etiologia , Linfoma de Zona Marginal Tipo Células B/patologia , Reto/cirurgia , Polipose Adenomatosa do Colo/patologia , Anastomose Cirúrgica , Colectomia , Humanos , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: An audit was undertaken to assess whether surgeons were informed of the readmission of their patients with postoperative deep venous thrombosis (DVT), or pulmonary embolus (PE). METHODS: A retrospective medical record review was conducted to detect patients who had an unplanned readmission in which DVT or PE formed part of the diagnosis and the first admission included a surgical procedure. The readmission was to John Hunter Hospital, Newcastle, Australia, a major tertiary referral teaching hospital, and the first admission was to any acute care hospital. The main outcome measures were: (i) hospital and specialty of the admitting doctor, (ii) the type of surgery performed, (iii) the length of time between admissions and (iv) the patient's previous medical history. The medical record was reviewed for documented evidence that the surgeon who performed the procedure was aware of the readmission. RESULTS: Of the 215 patient reviewed, 34 were classified as unplanned readmissions following a surgical procedure. Twenty-four patients (70.6%) were readmitted under a different specialty, three (8.8%) patients were readmitted under the same specialty but under a different surgeon, and seven (20.6%) patients were readmitted under the same surgeon. Of the 27 patients admitted under a different consultant, only 12 (44.4%) had documented evidence that the previous surgeon was aware of the readmission. CONCLUSION: The rate of DVT/PE complications following surgery is underestimated. This may lead to a reduced emphasis in DVT/PE prophylaxis in the mistaken belief that DVT/PE frequency is rarer than it is. Improved communication between teams is necessary to improve care.
Assuntos
Cirurgia Geral , Relações Interprofissionais , Readmissão do Paciente , Complicações Pós-Operatórias , Embolia Pulmonar/etiologia , Trombose Venosa/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Comunicação , Feminino , Humanos , Tempo de Internação , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Embolia Pulmonar/tratamento farmacológico , Procedimentos Cirúrgicos Operatórios , Trombose Venosa/tratamento farmacológico , Varfarina/uso terapêuticoRESUMO
OBJECTIVE: Naringenin, a naturally occurring flavonoid found in citrus fruits, is known to have anticarcinogenic properties. We have examined the effect of Naringenin on cell proliferation of an HT-29 colon cancer cell line. METHODS: HT-29 colon cancer cells were cultured in 96-well tissue culture plates. Naringenin concentrations ranging from 0.02 to 2.85 mmol were added to the wells of the Test group. The Control group contained all the elements present in the Test group with the exception of Naringenin. Cell proliferation was measured by colourimetric assay using the 2% WST-1 cell proliferation kit. RESULTS: Significant inhibition of cell proliferation was observed in HT29 colon cancer cells exposed to Naringenin at doses greater than 0.71 mmol. CONCLUSIONS: These results suggest a potential role for citrus fruits as a source of chemoprotective agents for colon cancer.
Assuntos
Adenocarcinoma/patologia , Antineoplásicos/farmacologia , Neoplasias do Colo/patologia , Flavanonas , Flavonoides/farmacologia , Divisão Celular/efeitos dos fármacos , Citrus/química , Células HT29/efeitos dos fármacos , Células HT29/patologia , HumanosRESUMO
Peutz-Jeghers syndrome (PJS) is a rare cancer predisposition, which is characterized by the presence of hamartomatous polyposis and mucocutaneous pigmentation. A significant proportion of both familial and sporadic forms of this disorder are associated with mutations in the STK11 (serine/threonine kinase 11)/LKB1 gene. In this report we present a series of Australian PJS cases, which suggest that mutations in the STK11 gene do not account for many families or patients without a family history. The most likely explanation is either the presence of another susceptibility gene or genetic mosaicism in the non-familial patients.